The overall objective is the design and synthesis of site-specific heterobifunctional protein-DNA and interhelical DNA-DNA crosslinking reagents for use as molecular tools for determining the tertiary structure of biologically important macromolecules. Specifically the first objective of this project is (a) the syntheses of heterobifunctional cleavable photolabile protein-nucleic acid crosslinking reagents, (b) development of a simple in vitro assay for screening these reagents, and (c) use of these reagents in collaboration with molecular biologists as in vivo probes (molecular tools) for the study of protein-nucleic acid complexes. A second objective of this project is (a) the syntheses of interhelical nucleic acid-nucleic acid crosslinking reagents, (b) development of a simple in vitro assay for screening these reagents and (c) use of these reagents in collaboration with molecular biologists on viruses and condensed chromatin as probes of the ultrastructure of packaged nucleic acid.